Is pulmonary artery a dose-limiting organ at risk in non-small cell lung cancer patients treated with definitive radiotherapy?

Abstract

PurposeOur previous study suggested that some pulmonary artery (PA) dosimetric parameters were associated with mortality in unresectable non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. The present study aims to analyze the impact of both PA and heart dosimetric parameters on survival of patients with NSCLC treated with definitive conventional fractionated radiotherapy (CFRT) in another independent research center and further determine whether the PA should be considered a dose-limiting organ at risk (OAR) for patients receiving thoracic CFRT.MethodsWe performed a retrospective analysis of successive patients with medically inoperable or unresectable NSCLC treated with definitive radiotherapy or chemoradiotherapy from August 2010 to September 2014. Clinical and pathological information, PA and heart dosimetric factors, and follow-up data were collected from each patient’s records and evaluated as potential prognostic factors for survival. Survival probabilities were estimated by the Kaplan-Meier method and compared by the log rank test. Cox proportional hazards regression models were performed to determine the independent predicators of survival. The optimal cutoff points of continuous dosimetric variables were determined by Youden index in receiver operating characteristic (ROC) analysis.ResultsThis study analyzed the records of 141 patients, 50.4% had adenocarcinoma, 71.6% had stage III disease, and 55% patients received concurrent chemoradiotherapy. Radiation dose ranged from 60 to 76 Gy in 30–38 fractions. Median follow up was 16.9 months. Median overall survival (OS) was 20.5 months (95% confidence interval [CI] 10.3-30.7 months), and 1-, 2-, 3-year OS rates were 75.2%, 58.2% and 56%, respectively. Univariate and multivariate analysis showed that Karnofsky Performance Status (KPS) score, Charlson’s Comorbidity Index (CCI), T and N stage, PA invasion grade and the percentage of PA volume that received 40 to 55 Gy (PA V40-55) were significantly associated with OS. No significant associations were found between heart dosimetric factors and OS. Median OS of patients with PA invasion grade 0, 1, 2, and 3 were 41.8, 27.8, 12.7 and 7.5 months, respectively (P < 0.001). PA V40, V45, V50 and V55, using thresholds of 80%, 68%, 45%, and 32%, respectively, were independent predictors for OS.ConclusionsPA invasion grade and PA V40-55 appear associated with OS in patients with NSCLC treated with definitive CFRT. We propose that PA be considered as a dose-limiting OAR for such patients.

Cardiac Toxicity of Thoracic Radiotherapy: Existing Evidence and Future Directions

“…Figure 2 reveals the different cardiac substructures that have been found to be significantly associated with cardiac events or mortality in patients having radical radiotherapy for lung cancer. 20 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 A number of studies point to dose received by cardiac substructures at the base of the heart as being associated with reduced survival or cardiac events. The base of the heart is defined anatomically as posterior to the sternum, at the level of the third costal cartilage.…”

Novel Methodology to Investigate the Effect of Radiation Dose to Heart Substructures on Overall Survival

“…1 Additional publications that followed the reporting of RTOG 0617 have explored retrospective and clinical trial data to develop a better understanding of the influence of cardiac dose on overall survival after radiation therapy. [2][3][4][5][6][7][8][9][10][11][12][13] A pooled analysis of 112 patients with NSCLC in clinical trials identified heart mean dose as being independently associated with cardiac events after treatment. Cardiac events were observed in 23% of the patients for whom the mean dose to the heart was identified as a predictor in multivariable analysis, including correcting for baseline cardiac risk.…”

“…Risk of a cardiac event for patients with a mean heart dose of <10 Gy, 10 to 20 Gy, or >20 Gy was 4%, 7%, and 21%, respectively, adjusted for competing risk. 13 Retrospective analyses have highlighted the V40-55 dose to pulmonary artery 9 and high dose to the left atrium and superior vena cava 3 as being associated with early mortality. In addition, changes in electrocardiograms (ECGs) were observed owing to the large dose to the left atrial wall.…”

Dose surface maps of the heart can identify regions associated with worse survival for lung cancer patients treated with radiotherapy

“…In 2015, the results from RTOG 0617 showed radiation dose to the heart, in lung cancer patients, was associated with worse overall survival [1] . Since the publication of RTOG 0617 a number of papers have further analysed the impact of cardiac dose, with the majority of these papers analysing retrospective datasets from a single institution or data from clinical trials [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] . These studies were summarised in the 2019 review by Zhang et al [14] , which concluded that no consistent cardiac dosimetric parameters yet exist.…”

“…Additionally, the literature [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] investigates dose to cardiac volumes, where some sub-structures are located primarily on the surface of the heart. The coronary arteries originate from the ascending aorta and are located across the surface of the heart.…”